The purpose of this study will be to examine the influence of (1) alveolar hypoxia and (2) the progressive development of pulmonary edema upon pulmonary capillary morphology. The first major aim of this study will be to examine the influence of alveolar hypoxia capillary morphology in isolated, perfused, pig lungs. These will be ventilated so that one part of the lung receives a PIO2 of either 100, 50, 25, or 0 mm Hg . Blood flow as well as ventilation/perfusion distributions will be obtained by the inert gas elimination technique. After a given period of ventilation, the lungs will be rapidly frozen at different Ptp, preserved by freeze substitution, and examined by TEM. Measurements of capillary morphology will be conducted in an effort to test the theory that the alveolar wall responds actively to hypoxia. The influence of edema upon capillary morphology will be examined as follows. Hemodynamic pulmonary edema will be induced by elevation of venous pressure in isolated, perfused dog lungs. The lungs will be allowed to gain weights equivalent to 30, 50, 75, 100 and 200% of their weight at excision. Thus, we will have lungs with pure interstitial edema to full-blown alveolar flooding. These lungs will be rapidly frozen under Zone 3 conditions (Part greater than Pven greater than Palv) at different transpulmonary pressures. Frozen samples will be obtained, preserved by freeze substitution, and examined by transmission electron microscopy. Measurements of capillary morphology will be made to gain a better understanding of how different phases of edema can influence pulmonary vascular resistance at the capillary level. In addition, I will correlate the presence of cellular vesicles to investigate the possible link between these and transcellular transport during edema. The results obtained from these experiments should enable us to better understand how edema and hypoxia, both major clinical problems, influence the distribution of perfusion in the lung. This should improve our management of patients with lung and heart disease.